Research Title: Effect of explant type and different plant growth regulators on callus induction and growth in citrus sinensis (l.) osbeck.

Author: Sahar Majdi Jaffal, Published Year: 2022

South Western Journal of Horticulture, Biology and Environment, 13(1), 1-12.

Faculty: Science

Abstract: In this study, we analyzed the effect of using different explants (zygotic embryos, leaves, stems, and cotyledons) on callus induction and the effect of different PGRs on the growth response of the callus. The results showed that callogenesis was faster when all explants were incubated in the dark than in light incubation. Maximum callus induction was observed in zygotic embryos (compared to other explants) and in the group cultured in 3 mg/L 2,4 D and 1 mg/L 6- BAP combination. Similarly, 3 mg/L 2,4 D and 1 mg/L BAP PGRs were also the effective concentrations for callus induction from cotyledons and leaves. However, a 2 mg/L 2,4 D and 1 mg/L BAP combination was the most potent in inducing callus from stems. In addition, our results indicated that the best hormonal combination for callus multiplication of callus derived from zygotic embryos was 1 mg/L 2,4 D and 1 mg/L BAP. The inhibition of ethylene activity improved callus growth during the multiplication stage in two groups being treated with 1 mg/L 2,4 D alone or with 2 mg/L 2,4 D in combination with 1 mg/L BAP. In contrast, ethylene synthesis inhibitors had insignificant effects on callus multiplication in any of the groups cultured in different PGRs combinations. The calluses obtained in all treated groups were friable, loose, and had a white to yellow color.

Keywords: Citrus sinensis, 6-benzyl amino purine, 2,4 dichloro phenoxy acetic acid, callus, ethylene.

Research Title: Evaluation of the antiproliferative effect of selected plant extracts on colon and skin cancer cell lines.

Author: Sahar Majdi Jaffal, Published Year: 2022

Journal of Applied Pharmaceutical Science, , 12 (11):91-96.

Faculty: Science

Abstract: The aim of this study was to assess the antiproliferative effect of extracts obtained from medicinal plants that grow wild in Jordan against the human melanoma (WM136-1A) and colon cancer (Caco-2 cancer) cell lines using fibroblast cell lines as control cells. The selected plants are Varthemia iphionoides (Asteraceae), Micromeria myrtifolia (Lamiaceae), Micromeria nervosa (Lamiaceae), Origanum dayi (Lamiaceae), Ajuga chia (Lamiaceae), Salvia palaestina (Lamiaceae), and Bongardia chrysogonum (Berberidaceae). The results showed that M. nervosa and O. dayi exhibited antiproliferative activity against Caco-2 cancer cell line, with half-maximal inhibitory concentrations (IC50) that equal 98 ± 2.5 and 73.6 ± 3.4 μg/ml, respectively. Furthermore, A. chia, B. chrysogonum, and O. dayi exhibited antiproliferative activity against the WM136-1A cancer cell line, with IC50 that equals 400 ± 5.1, 98.1 ± 3.2, and 245 ± 3.6 μg/ml, respectively. None of the extracts had an effect on fibroblast cells at any used concentration. In conclusion, the extracts of M. nervosa, O. dayi, A. chia, and B. chrysogonum showed promising antiproliferative potential and can be good candidates for the development of novel anticancerous agents.

Keywords: Medicinal plants, Jordan, anti-proliferation

Research Title: Imbalances of key parameters needed for energy-yielding processes in the serum of tramadol-treated male rats.

Author: Sahar Majdi Jaffal, Published Year: 2022

Journal of applied pharmaceutical Science, 12(4): 153-158.

Faculty: Science

Abstract: Addiction is one of the major health challenges in the world. Tramadol is an analgesic that has been widely abused, causing negative health consequences. This study sheds light on the effect of the administration of tramadol hydrochloride (HCl) on the serum levels of key parameters needed for energy production. Male Wistar rats received oral administration of tramadol HCl for 30 days and then were sacrificed to collect blood from the eyes and determine the levels of nutritional measures in the serum by kits. Our findings showed that the daily oral gavage of 50 or 100 mg/kg tramadol HCl for a month decreased the serum levels of ferrous iron and glucose significantly compared to the nontreated rats. Additionally, both doses increased the levels of total protein, triglycerides, and magnesium compared to the nontreated animals. Only the dose of 50 mg/kg tramadol HCl was effective in elevating the serum concentration of vitamin B12. Moreover, tramadol HCl treatment did not trigger any change in the levels of zinc in comparison to the control group. In conclusion, tramadol causes imbalances of key parameters needed for energy production.

Keywords: Addiction, tramadol, rats, energy

Research Title: The role of adenosine receptor ligands on inflammatory pain: Possible modulation of TRPV1 receptor function.

Author: Sahar Majdi Jaffal, Published Year: 2023

Inflammopharmacology, 31: 337-347.

Faculty: Science

Abstract: Chronic pain has a debilitating consequences on health and lifestyle. The currently available analgesics are often ineffective and accompanied by undesirable adverse effects. Although adenosine receptors (AR) activation can affect nociceptive, inflammatory, and neuropathic pain states, the specific regulatory functions of its subtypes (A1, A2A, A2B and A3 ARs) are not fully understood. The aim of this study was to investigate the role of different AR ligands on inflammatory pain. The von Frey filament test was used to assess the anti-nociceptive effects of adenosine ligands on Complete Freund’s Adjuvant (CFA)-induced mechanical allodynia in (180–220 g) adult male Sprague Dawley rats (expressed as paw withdrawal threshold, PWT). Neither the A2AAR selective agonist CGS 21680 hydrochloride (0.1, 0.32 and 1 mg/kg) nor the A2BAR selective agonist BAY 60-6583 (0.1, 0.32 and 1 mg/kg) produced any significant reversal of the PWT. However, the A1AR selective agonist ( ±)-5′-Chloro-5′-deoxy-ENBA, the A3AR selective agonist 2-Cl-IB-MECA, the A2AAR selective antagonist ZM 241385 and the A2BAR selective antagonist PSB 603 produced a significant reversal of the PWT at the highest dose of 1 mg/kg. Co-administration of the selective antagonists of A1AR and A3AR PSB36 (1 mg/ml) and MRS-3777 (1 mg/ml); respectively, significantly reversed the anti-nociceptive effects of their corresponding agonists. Furthermore, calcium imaging studies reveled that the effective AR ligands in the behavioral assay also significantly inhibit capsaicin-evoked calcium responses in cultured rat dorsal root ganglia (DRG) neurons. In conclusion, modulating the activity of the transient receptor potential vanilloid 1 (TRPV1) receptor by ARs ligands could explain their anti-nociceptive effects observed in vivo. Therefore, the cross talk between ARs and TRPV1 receptor may represent a promising targets for the treatment of inflammatory pain conditions.

Keywords: CFA, inflammation, chronic, pain TRPV1

Research Title: Substance Abuse among University Students: Assessing Prevalence, Risk and Preventive Measures.

Author: Sahar Majdi Jaffal, Published Year: 2023

Jordan Journal of Pharmaceutical Science, 16(2): 235-244.

Faculty: Science

Abstract: The study included a survey conducted among 679 students from private and public universities whereby two third of them were females and more than half were studying in medical and health departments. It was found that 7.1% of university students used drugs in their life including illicit drugs, alcohol and cigarettes. Also, the addictive students started using drugs at a mean age of 18 years old ± 3.9. Importantly, around half of the addictive students succeeded to quit using drugs, 20.8% reported not trying to quit, while 33.3% of them tried but could not quit. In addition, the findings of this study revealed that peer pressure (n= 657, 96.8%), and the lack of religious commitment (n= 654, 96.3%), were the most motivational factors for drug abuse. Finally, regression analysis showed that female gender (OR= 0.094, p-value <0.001), and studying in public university (OR= 0.496, p-value= 0.042) were considered protective factors against substance abuse.

Keywords: Students, substance use, knowledge, attitude

Research Title: Effect of Arbutus andrachne L. Methanolic Leaf Extract on TRPV1 Function: Experimental and Molecular Docking Studies.

Author: Sahar Majdi Jaffal, Published Year: 2022

Journal of Applied Pharmaceutical Science, 12(10): 69-77

Faculty: Science

Abstract: Currently used analgesics have several side effects urging the need for new natural sources of therapeutics. Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel and a key receptor in pain. In this study, we explored the effect of a methanolic leaf extract from Arbutus andrachne L. (a medicinal plant growing in Jordan) and its mechanism of action on TRPV1 function and expression. Our findings showed that the extract decreased capsaicin-induced cobalt (Co+2) influx in dorsal root ganglia (DRG) neurons, an effect that involved cannabinoid receptor 1 (CB1) and TRPV1 but not alpha (α)-2 adrenergic receptors. The extract had no effect on capsaicin-evoked TRPV1 expression in the skin, DRGs, spinal cord, and brain. Importantly, the effect of A. andrachne was similar to the responses shown in the positive control group. Additionally, by conducting molecular docking between the ingredients identified in A. andrachne extract and TRPV1 receptor, it was found that α-tocopherol, ursolic acid, and β-sitosterol (similar to TRPV1 antagonist, capsazepine) fit in the same pocket of TRPV1 receptor indicating that these compounds are the active ingredients responsible for the effect of the extract in decreasing capsaicin-induced Co+2 influx. A. andrachne extract decreased capsaicin-induced Co+2 influx significantly and can be a good candidate as an analgesic.

Keywords: Arbutus andrachne, TRPV1, molecular docking, cobalt, influx

Research Title: Medicinal Plants of Jordan Possessing Anti-Nociceptive, Anti Inflammatory and Antipyretic Properties.

Author: Sahar Majdi Jaffal, Published Year: 2023

Archives in traditional and complementary medicine, 2(1): 1-14.

Faculty: Science

Abstract: Since ancient period, man depended on the surrounding environment for survival and used plants for thetreatment of diseases. To date, there is increasing trend towards exploring the effects of medicinal plantsas they are affordable, cheap, and availableand have fewerside effects. Earlier reports showed thatseveral plants are used in folk medicine for the treatment of different diseases and disorders. Medicinalplants are rich in flavonoids, alkaloids, tannins, triterpenes, polysaccharides, phenolic acids, organicacids,fatty acids,vitaminsandcarotenoids.The activeingredientsfrom herbsarevaluedasrawmaterials in herbal preparations and modern medicines. Jordan is one of the countries that are rich inflora in general and in medicinal plants in particular due to its geographic and climatic diversity. Thereare 363 medicinal plants in Jordan. The effect of some of these plants was proved scientifically invariableexperimentsdoneindifferentcountries.LiteraturesearchfromPubmedandGooglescholarwas conducted for articles in this context. The aim of this review was to highlight the researches thatproved the anti-nociceptive, anti-inflammatory and antipyretic properties of medicinal plants in JordanandlistmultipleusesofmedicinalplantsbyJordanianpractitioners.Summarizing these studies is of vital importance to direct the attention of researchers towards medicinalplantsthatareusedintraditionalmedicinewhiletheireffectswerenotdeterminedscientifically.Discoveringneweffectsformedicinalplantsisanassetforpharmaceutical industryand theworld trade

Keywords: Jordan;medicinalplants;nociception;inflammation;pyrexia

Research Title: Interaction of the synthetic cannabinoid WIN55212 with tramadol on nociceptive thresholds and core body temperature in a chemotherapy-induced peripheral neuropathy pain model

Author: Sahar Majdi Jaffal, Published Year: 2023

Neuroreport, 34(8), 441–448.

Faculty: Science

Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant adverse effect of many anticancer drugs. Current strategies for the management of CIPN pain are still largely unmet. The aim of this study is to investigate the antinociceptive potential of combining tramadol with the synthetic cannabinoid WIN55212, and to evaluate their associated adverse effects, separately or in combination, in a CIPN rat model, and to investigate their ability to modulate the transient receptor potential vanilloid 1 (TRPV1) receptor activity. Von Frey filaments were used to determine the paw withdrawal threshold in adult male Sprague-Dawley rats (200-250 g) following intraperitoneal (i.p) injection of cisplatin. Single cell ratiometric calcium imaging was used to investigate WIN55212/tramadol combination ability to modulate the TRPV1 receptor activity. Both tramadol and WIN55212 produced dose-dependent antinociceptive effect when administered separately. The lower dose of tramadol (1 mg/kg) significantly enhanced the antinociceptive effects of WIN55212 without interfering with core body temperature. Mechanistically, capsaicin (100 nM) produced a robust increase in [Ca 2+ ] i in dorsal root ganglia (DRG) neurons ex vivo . Capsaicin-evoked calcium responses were significantly reduced upon pre-incubation of DRG neurons with only the highest concentration of tramadol (10 µM), but not with WIN55212 at any concentration (0.1, 1 and 10 µM). However, combining sub-effective doses of WIN55212 (1 µM) and tramadol (0.1 µM) produced a significant inhibition of capsaicin-evoked calcium responses. Combining WIN55212 with tramadol shows better antinociceptive effects with no increased risk of hypothermia, and provides a potential pain management strategy for CIPN.

Keywords: cannabinoid, pain, DRG, CIPN

Research Title: Role of TRPV1 in health and disease.

Author: Sahar Majdi Jaffal, Published Year: 2023

Faculty: Science

Abstract: Transient receptor potential vanilloid 1 (TRPV1) channel is a non-selective cation channel that plays a pivotal role in pain transduction. However, more than a pain sensor, it is involved in an array of vital processes in different body systems. The findings of several studies illustrated that many disorders are associated with alterations in the function and/or expression of the TRPV1 channel. Accordingly, the TRPV1 channel has become an important target in numerous therapeutic interventions. Several TRPV1 antagonists are already in the market, however, there is a need for new drugs with fewer or no side effects. This review highlights the involvement of the TRPV1 channel in a plethora of physiological and pathological conditions and points to its importance as a therapeutic target.

Keywords: TRPV1, Expression, Function, Health, Disease, Target

Research Title: Effects of PGf2α On P-Erk1/2 Mapk Activation, Proliferation and Formation of Trans-Endothelial Tunnels in Swiss 3t3 Fibroblast Cells

Author: Sahar Majdi Jaffal, Published Year: 2023

Faculty: Science

Abstract: Fibroblast cells are key cells that play a pivotal role in maintaining hemostasis in the body. Keeping the balance between proliferation, differentiation and apoptosis of fibroblast cells is fundamental for the role of these cells. Many mediators can increase fibroblasts' proliferation including prostaglandin F2α [PGF2α]-induced phosphorylated extracellular signal regulated kinase [p-ERK1/2] mitogen activated protein kinase [MAPK]. Thus, the effects and mechanisms of PGF2α in p-ERK1/2 MAPK activation, proliferation and the cytoskeleton of fibroblast cells were explored in the current study. The results showed that sustained p-ERK1/2 MAPK activation was dependent on MAP kinase kinase [MEK-1], proto-oncogene non-receptor tyrosine kinase [c-Src], protein kinase C [PKC] and insulin like growth factor-1 receptor [IGF1R]. The transient p-ERK1/2 MAPK activation involved c-Src, phosphatidylinositol 3-kinase [PI3K]/AKT and PKC pathways. Further, Gαq but not Gαi was involved in the activity of PGF2α in inducing p-ERK1/2 MAPK activation at all time points. In contrast, p-ERK1/2 MAPK activation evoked by PGF2α did not involve Rho, Rho-associated protein kinase [ROCK], adenylyl cyclase [AC], the mammalian target of rapamycin [mTOR] or epidermal growth factor receptor [EGFR]. Notably, PGF2α increased fibroblasts' proliferation via PI3K, MEK1, c-Src, PKC and IGF1R but not EGFR, Gαi, AC or mTOR pathways suggesting a correlation between proliferation and pathways that are involved in the transient and sustained p-ERK1/2 MAPK activation or in the sustained phase alone. Additionally, PGF2α produced a noticeable change in the cytoskeleton of fibroblast cells and increased the number of trans-endothelial tunnels by 54.12% compared to control group. These findings provide further insights into the mechanisms of PGF2α in p-ERK1/2 MAPK activation, proliferation and the cytoskeleton of swiss 3t3 fibroblast cells and can open an avenue to conduct more researches on PGF2α signalling to tailor drugs that can prevent specific routes in PGF2α-FP signalling pathways and decrease fibroblasts' proliferation.

Keywords: Fibroblasts; proliferation; PGF2α; FP receptor; trans-endothelial tunnels; p-ERK MAPK